The prokineticin receptor agonist Bv8 decreases IL-10 and IL-4 production in mice splenocytes by activating prokineticin receptor-1.
BACKGROUND
Bv8, prokineticin-1, or endocrine gland-vascular endothelial growth factor, and prokineticin-2 are recently isolated peptide agonists of two G protein-coupled receptors, prokineticin receptor-1 (PROKR 1) and PROKR 2, and have been described as affecting a number of myeloid cell functions. We evaluated the impact of Bv8 on lymphoid cells by investigating its ability to modulate T cell cytokine balance in mouse.


RESULTS
The production of T-helper1 cytokines (IL-2, IFN-gamma and IL-1beta), the T-helper 2 cytokine IL-4, and the anti-inflammatory cytokine IL-10 by mouse splenocytes was evaluated after polyclonal stimulation or immunisation with the keyhole limpet hemocyanin protein antigen by measuring cytokine levels. When added in vitro to Con-A-stimulated splenocytes, Bv8 significantly increased IL-1beta and decreased IL-4 and IL-10; IL-2 and IFN-gamma were not affected. Similar results were obtained when Bv8 was administered in vivo. In KLH-immunised mice, splenocytes restimulated in vitro with KLH and Bv8 produced significantly smaller amounts of IL-4 and IL-10. KLH-induced IL-10 and IL-4 production was also significantly blunted in animals administered Bv8 in vivo at the time of KLH immunisation or two weeks later. The Bv8-induced effects were lost in mice lacking the PROKR 1 gene, thus indicating that PROKR 1 is the receptor involved in the modulation of cytokines.


CONCLUSIONS
These findings indicate that Bv8/prokineticin-1 is a novel modulator of lymphoid functions, and may be a suitable target for new immunopharmacological strategies.
Franchi
Silvia
S
Department of Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milano, Italy. silvia.franchi@unimi.it
Giannini
Elisa
E
Lattuada
Donatella
D
Lattanzi
Roberta
R
Tian
Hui
H
Melchiorri
Pietro
P
Negri
Lucia
L
Panerai
Alberto E
AE
Sacerdote
Paola
P
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D006433:Hemocyanins / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000494:pharmacology*
D007375:Interleukin-1; C525015:PKR1 protein, mouse; C525016:PKR2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin